TY - JOUR
T1 - Strategies for Glycoengineering Therapeutic Proteins
AU - Dammen-Brower, Kris
AU - Epler, Paige
AU - Zhu, Stanley
AU - Bernstein, Zachary J.
AU - Stabach, Paul R.
AU - Braddock, Demetrios T.
AU - Spangler, Jamie B.
AU - Yarema, Kevin J.
N1 - Funding Information:
This work was supported by the National Institutes of Health (R01EB029455, R01CA240339, R21CA249381, and R01CA112314 and the Cohen Translation Fund (JHU).
Publisher Copyright:
Copyright © 2022 Dammen-Brower, Epler, Zhu, Bernstein, Stabach, Braddock, Spangler and Yarema.
PY - 2022/4/13
Y1 - 2022/4/13
N2 - Almost all therapeutic proteins are glycosylated, with the carbohydrate component playing a long-established, substantial role in the safety and pharmacokinetic properties of this dominant category of drugs. In the past few years and moving forward, glycosylation is increasingly being implicated in the pharmacodynamics and therapeutic efficacy of therapeutic proteins. This article provides illustrative examples of drugs that have already been improved through glycoengineering including cytokines exemplified by erythropoietin (EPO), enzymes (ectonucleotide pyrophosphatase 1, ENPP1), and IgG antibodies (e.g., afucosylated Gazyva®, Poteligeo®, Fasenra™, and Uplizna®). In the future, the deliberate modification of therapeutic protein glycosylation will become more prevalent as glycoengineering strategies, including sophisticated computer-aided tools for “building in” glycans sites, acceptance of a broad range of production systems with various glycosylation capabilities, and supplementation methods for introducing non-natural metabolites into glycosylation pathways further develop and become more accessible.
AB - Almost all therapeutic proteins are glycosylated, with the carbohydrate component playing a long-established, substantial role in the safety and pharmacokinetic properties of this dominant category of drugs. In the past few years and moving forward, glycosylation is increasingly being implicated in the pharmacodynamics and therapeutic efficacy of therapeutic proteins. This article provides illustrative examples of drugs that have already been improved through glycoengineering including cytokines exemplified by erythropoietin (EPO), enzymes (ectonucleotide pyrophosphatase 1, ENPP1), and IgG antibodies (e.g., afucosylated Gazyva®, Poteligeo®, Fasenra™, and Uplizna®). In the future, the deliberate modification of therapeutic protein glycosylation will become more prevalent as glycoengineering strategies, including sophisticated computer-aided tools for “building in” glycans sites, acceptance of a broad range of production systems with various glycosylation capabilities, and supplementation methods for introducing non-natural metabolites into glycosylation pathways further develop and become more accessible.
KW - N-glycans
KW - biomanufacturing
KW - glycoengineering
KW - glycosylation
KW - pharmacodynamics
KW - pharmacokinetics
KW - therapeutic
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U2 - 10.3389/fchem.2022.863118
DO - 10.3389/fchem.2022.863118
M3 - Review article
C2 - 35494652
AN - SCOPUS:85128860887
SN - 2296-2646
VL - 10
JO - Frontiers in Chemistry
JF - Frontiers in Chemistry
M1 - 863118
ER -